text:
|Publication number
|Publication type
|Application number
|Publication date
|Jun 30, 2009
|Filing date
|Oct 20, 2006
|Priority date
|Oct 31, 2005
|Fee status
|Also published as
|Publication number
|Donghui Lu, Shuxin Zhou
|Original Assignee
|Innovative Bioceramix, Inc.
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (11), Non-Patent Citations (9), Referenced by (3), Classifications (57), Legal Events (3)
|External Links: USPTO, USPTO Assignment, Espacenet
This application claims the priority of Provisional Patent Application Ser. No. 60/731,561, filed Oct. 31, 2005.
a. Field of the Invention
The present invention relates generally to hydraulic cements for medical and dental applications, and, more particularly, to an aluminum-and magnesium-free hydraulic cement that produces a nano-dispersed composite of calcium-silicate-hydrate gel mixed with hydroxyapatite, that exhibits good mechanical strength and high biocompatibility and bioactivity.
b. Related Art
Hydraulic cements are commonly utilized in construction and also in medical and dental applications.
One of the most important hydraulic cements is calcium di-silicate and tri-silicate-based cement, which is widely used in construction. There are three main compounds in the cement: dicalcium silicate (C2S), tricalcium silicate (C3S), and calcium aluminate (C3A). Highly crystalline calcium hydroxide (Ca(OH)2) (referred to later as CH) and amorphous calcium-silicate-hydrate (C—S—H) are the principal phases that form in the hydration process of C2S and C3S. The hydrated cement paste consists of approximately 70% C—S—H and 20% CH, with additional phases including about 7% sulfoaluminate, and about 3% of secondary phases. The calcium hydroxide component, which is formed as a result of the setting reaction, negatively effects the quality of the set cement, since CH is soluble in water and has low strength.
Certain Portland cement—based materials (referred to as mineral trioxide aggregate, or MTA) have been used for medical and dental applications, such as endodontic dental treatment and the retention of cores [Vargas et al., "A Comparison of the In vitro Retentive Strength of Glass-Ionomer Cement, Zinc-Phosphate Cement, and Mineral Trioxide Aggregate for the Retention of Prefabricated Posts in Bovine Incisors" J. Endodont. 30(11) 2004, 775-777]. MTA, like Portland cement, consists primarily of tricalcium silicate, tricalcium oxide, and tricalcium aluminates. [Torabinejad et al. "Physical and chemical properties of a new root-end filling material". J Endodont 21(1995) 349-253]. The hydration product of calcium aluminates is a mixture of calcium-aluminate compounds and calcium-sulfate-aluminate compounds [Concrete, J. F. Young, pp76-98, Prentice-Hall, Inc, Englewood Cliffs, 1981].
MTA, has been used in many surgical and non-surgical applications, and possesses the biocompatibility and sealing abilities requisite for a perforation material [Lee, et al, "Sealing ability of a mineral trioxide aggregate for repair of lateral root perforations" J Endod 1993; 19:541-4.]. It can be used both as a non-absorbable barrier and restorative material for repairing root perforations. Because it is a hydrophilic cement and requires moisture to set, MTA has been the barrier of choice when there is potential for moisture contamination, or when there are restrictions in technical access and visibility during the restorative process. MTA also has good compressive strength after setting.
In one example, Torabinejad et al (U.S. Pat. Nos. 5,415,547, and 5,769,638) disclosed an improved method for filling and sealing tooth cavities which involved the use of an MTA cement composition, including the ability to set in an aqueous environment. The cement composition comprises Portland cement, or variations on Portland cement, which exhibits physical attributes sufficient to form an effective seal against re-entrance of infectious organisms. However, the MTA composition derived from Portland cement is gray in color, which is unsuitable for many dental applications. Moreover, among other problems, MTA contains significant amounts of aluminum and consequently presents certain biocompatibility and toxicity concerns, as will be discussed below.
Primus (U.S. Pat Appl. 20030159618) disclosed a process for making a white, substantially non-iron containing dental material formed from Portland cement. The material, also referred to as White MTA or WMTA, may be used as a dental cement, dental restorative or the like. However, this process only decreases the iron content and does not improve the biological properties of the material, since it still contains aluminum.
A number of investigators have reported improvement of mechanical strength of Portland cement by adding silica fume (SiO2, referred later as S) in order to decrease Ca(OH)2 content in the hydrated cement [Mitchell, Et Al, "Interaction Of Silica Fume With Calcium Hydroxide Solutions And Hydrated Cement Pastes", Cement And Concrete Research (1998), 28(11), 1571-1584 And Persson "Seven-Year Study On The Effect Of Silica Fume In Concrete" Advanced Cement Based Materials (1998), 7(3/4), 139-155]. The mechanism depends on the silica fume reacting with the calcium hydroxide CH to produce an amorphous C—S—H gel having a high density and low Ca/Si ratio. This demonstrates that removal of CH can make for substantial improvement of the set cement.
The foregoing effect was also recognized in Japanese patent no. JP 11-292600 "Production of slightly calcium leaching cement composition." (Oct. 26, 1999). The patent disclosed a "slightly calcium leaching Portland cement composition" with a phosphate or fluorides added to the cement material (e.g. Portland cement). The resulting product is a cement hydrate with reduced production in calcium hydroxide and an increase of calcium phosphate compounds, e.g. hydroxyapatite. The material is designated for treatment of hazardous wastes, such as nuclear waste, to prevent leaching, and also for construction materials and structural materials, which would include relatively high levels of impurities and consequently exhibit toxicity unsuitable for medical/dental use. Moreover, when Portland cement is combined with "phosphoric acid compounds" or fluorides, aluminum phosphate or aluminum fluoride result. Aluminum compounds are therefore present in this material as well, similar to the situation with MTA.
The presence of aluminum is a major disadvantage of the materials derived from Portland cement (such as MTA or WMTA) when used for biomedical and dental applications. Aluminum ions will be released into human biological system during hydration and setting reaction of such cement. Moreover, in the case of permanent and long term applications, such as dental filling, bone implants, and use in orthopedic surgery, the calcium sulfate aluminates in the cements will continually release aluminum ions into the human biological system [Fridland, et al., "MTA Solubility: A Long Term Study", JOE—Volume 31, Number 5, May 2005, and JOURNAL OF ENDODONTICS, VOL. 29, NO. 12, DECEMBER 2003].
Research indicates that aluminum ions are toxic to the human biological system. For example, aluminum inhibits mineralization of bone, and is toxic to osteoblasts. Diseases that have been associated with aluminum include dialysis dementia, renal osteodystrophy and Alzheimer's disease. Aluminum also has adverse effect on red blood cells, parathyroid glands and chromosomes. Accumulation of aluminium in the body tends to occur when the gastrointestinal barrier is circumvented, as is the case with implants or dental treatments. See for example, Monteagudo, et al., "Recent developments in aluminum toxicology", Medical toxicology and adverse drug experience (1989 January-February), 4(1), 1-16. Ref: 158; Rodriguez, et al., "Aluminum administration in the rat separately affects the osteoblast and bone mineralization", J Bone Miner Res 1990 January;5(1):59-67; SAVARINO. et al., "In vitro investigation of aluminum and Fluoride release from compomers, conventional and resin-modi. Ed glass-ionomer cements: A standardized approach," J. Biomater. Sci. Polymer Edn, Vol. 11, No. 3, pp. 289-300 (2000). One commonly observed result of the awareness of aluminum toxicity to human bodies is the gradual elimination of aluminum cooking utensils from general (and in particular household) use, and their replacement by stainless steel utensils; this process continues despite the fact that aluminum utensils provide excellent heat transfer characteristics due to high thermal conductivity (up to 300 W/mK), as opposed to the relatively low thermal conductivity (and significantly higher cost) of stainless steel.
All of the prior cement compositions discussed above are based on (or derived from) Portland cement, and as such rely on aluminum compounds to achieve early strength when setting. If the aluminum were to be removed from such compositions, the strength increase would be much slower, rendering the cement useless for its intended applications. As will be described below, the hydraulic cement of the present invention does not use aluminum, and instead, employs inventive materials science (e.g., inclusion of kinetics-accelerating phosphate compounds) and processing methods (e.g., controlled particle size) to achieve early setting strength without aluminum compounds.
There are instances reported in the literature where phosphates have been combined with calcium-silicate Portland-type cements. For example Ma et al ["Effect of phosphate additions on the hydration of Portland cement" Advances in Cement Research (1994), 6(21), 1-12] discussed the effect of phosphate additions on the hydration process of Portland cement. The phosphate-modified cements, which were not designed for biomedical applications, produced more hydration heat and exhibited faster hydration rates than the reference ordinary Portland cement. The reaction products were amorphous, but hydrothermal treatment at 160� C. of ordinary Portland cement (OPC) modified by CaHPO4 allowed transformation of a poorly crystalline phosphate phase into hydroxyapatite, resulting in improved flexural strengths. A number of disadvantages limit the applications of the process, such as the need for hydrothermal treatment for formation of the hydroxyapatite, and the need for high pressure (28 MPa) pressing in order to achieve an adequately high strength. Also, the process described by Ma et al can not be used for forming a uniform composite structure, and the mechanical strength was not significantly improved by comparison with Ordinary Portland cement (OPC). Moreover, the cements still relied on aluminum compounds to gain early strength. Recently, U.S. Pat. No. 7,083,672 (Wagh et al) disclosed phosphosilicate ceramics comprising 65-85 weight percent of a powder and about 15-35 weight percent of a liquid, which are combined to form a paste for various uses, for example, as a bone cement for dental and orthopedic purposes. The powder component comprises a "sparsely soluble oxide" powder, such as magnesium oxide powder, monovalent alkali metal phosphate powder and a sparsely soluble silicate powder (e.g. CaSiO3). The liquid component comprises a pH modifying acid (e.g. Ca(H2PO4)2H2O), such that pH is in the range of 3-7 (preferably nearly 3) during setting of the cement. Hydroxyapatite (HAP) powder may be introduced into the composition by admixing an HAP powder into the other powder; there is no provision for reactive, in-situ formation of HAP, which limits the possibilities of composite formation, and also provides less than satisfactory mechanical properties and bioactivity/biocompatibility in the set material.
Chemically bonded ceramics (CBC) in the system CaO—SiO2—P2O5—H2O were investigated by Hu et al ["Investigation of hydration phases in the system CaO—SiO2—P2O5—H2O" J. Mater. Res. 1988, 3(4) 772-78] and Sterinke et al [Development of chemically bonded ceramics in the system CaO—SiO2—P2O5—H2O" Cement and Concrete Res. 1991 (21)66-72]. The powders of CBC were synthesized by sol-gel process and then fired at a temperature of 700-1000 C for 2 hours. The components of the powders before hydration are calcium hydroxyapatite (major), di-calcium silicate, γ-2CaO—SiO2, amorphous calcium silicate, and amorphous calcium phosphate [Hu, et al, "Studies of strength mechanism in newly developed chemically bonded ceramics in the system CaO—SiO2—P2O5—H2O" Cement and Concrete Res. 1988 (18)103-108]. However, the mechanical properties were not improved when the samples were hydrated at room temperature. In order to increase the mechanical strength of CBC, the samples were made with high pressure formation (345 MPa) and were subsequently hydrated at high temperatures.
Calcium phosphate cement (CPC) was first reported in a binary system containing tetracalcium phosphate (TTCP) and dicalcium phosphate anhydrate (DCPA) [L. C. Chow et al. J. Dent Res., 63, 200, 1984]. The advantages of CPC include self-setting (similar to OPC), plus an apatitic phase in the set cement (e.g. HAP, or other similar phases of varying chemistry and crystallinity). Consequently, CPC is a bio-active material that interract with body fluids through a dissolution-reprecipitation process. This has led to applications such as bone replacement and reconstruction, and also drug delivery [M Dairra, et al. Biomaterials, 19 1523-1527, 1998; M. Otsuka, et al. J. of Controlled Release 43(1997)115-122, 1997, Y. Tabata, PSTT, Vol. 3, No. 3, 80-89, 2000; M. Otsuka, et al. J. of Pharm. Sci. Vol. 83, No. 5, 1994].
Calcium phosphate cement (CPC) is typically formulated as a mixture of solid and liquid components in pertinent proportions, which react to form the apatite. The physicochemical reactions that occur upon mixing of the solid and liquid components are complex, but dissolution and precipitation are the primary mechanisms responsible for the final apatite formation [C. Hamanish et al J. Biomed. Mat. Res., Vol. 32, 383-389, 1996; E. Ferandez et al J. Mater. Sci. Med. 10, 1999]. The reaction pathway in most CPC systems does not lead to stoichiometric HAP, but rather to calcium-deficient Ca10-x(HPO4)x(PO4)6-x(OH)2-x, similar to that found in bone. The process parameters, such as Ca/P ratio, powder/liquid ratio, seeds concentration type, and nature of reagents, control the final properties, such as phase content, porosity, strength, setting time, phase transformation kinetics, and microstructure of the CPC-derived hydroxyapatite (CPC-HAP). Synthetic CPC may also incorporate carbon-containing phases, similar to bone minerals.
Bermudez et al [J. Mat. Sci. Med. 4, 503-508, 1993; ibid 5, 67-71, 1994] correlated the compressive strength of CPC to the starting Ca/P ratio in systems of monocalcium phosphate monohydrate (MCPM) and calcium oxide. The major drawback of CPC technology is low mechanical strength (generally below 20 MPa compressive), which severely limits its suitability for medical/dental materials and devices. Intensive research continues on increasing strength of CPC, for example sophisticated processing methods involving reduction or elimination of flaws (such as voids or cracks) from set cement have been reported [T Troczynski, "Bioceramics-A Concrete Solution", Nature Materials, [3] 13-14, January 2004]. As CPC behaves as a typical brittle, flaw-sensitive ceramic, reduction of flaws translates to increased strength. However, substantial elimination of flaws in CPC setting in contact with living tissue such as bone or dentine may be impractical or impossible. In some situations it is also not desirable, as hard tissue such as bone may integrate easier with porous CPC as compared to dense CPC. There is constantly a continuing need to be able to increase strength of biological cements without substantial modification of their porosity or flaws density.
A combination of the oxides of calcium, phosphorous and silicon (with the major component being silica, in an amount of about 45 wt %) results in a bioactive glass material, providing excellent in-vivo performance and stimulation of cell growth, sometimes even better than hydroxyapatite or other calcium phosphates [e.g. Oonishi et al, "Particulate Bioglass compared with hydroxyapatite as a bone graft substitute", J. Clin. Orthop. Rel. Res. 334, 316-25, 1997; also U.S. Pat. No. 5,811,302 by Ducheyne et al, Sep. 22, 1988]. This is an indication that the biomaterials synthesized through combination of the three oxides of calcium, phosphorous and silicon may become even more bioactive than calcium phosphates that lack silica. This observation has been explored by partial replacement of Ca by Si in the solid solution through high-temperature treatment and sintering [e.g. compare US Pat. Appl. 20030003160, Jan. 2, 2003, S. M. Pugh et al, "Synthetic biomaterial compound of calcium phosphate phases particularly adapted for supporting bone cell activity"]. Unfortunately, although chemically advantageous, bio-glass must be processed at very high temperatures (generally in excess of 1000 C), and is a rather dense, weak and brittle material. Another disadvantage of bio-glass is that it does not easily dissolve in biological environments (due to dense SiO2 film coverage), which is desirable in some applications, e.g. for stimulation of bone growth.
The literature has recently reported attempts to address these issues, by combining the three oxides of calcium, phosphorous and silicon into porous crystalline composite material, which would possess a high bioactivity similar to the bio-glass, but which would be stronger (even though porous) and easier to resorb in-vivo [A. R. El-Ghannam, "Advanced bioceramics composite for bone tissue engineering: design principles and structure-bioactivity relationship", J. Biomed. Mater. Res. 69A, 490-501, 2004]. The precursors to the three oxides (plus sodium oxide) were heat treated at high temperatures (130-800 C) to result in a porous composite of crystalline silica (quartz or crystobalite), and variety of calcium-phosphates or calcium-sodium-phosphates. Excellent bioactivity of these composites was demonstrated. Unfortunately the need for the high temperature treatment makes this composite material difficult to apply as biomaterial, as all the processing and shaping operations must take place outside of the application site.
The advantages of the simultaneous presence of Ca, P, and Si elements in bioceramic materials has been also recognized through sinter-processing (high temperature heat treatment) of silicon substituted hydroxyapatite and other calcium phosphates [Alexis M Pietak, Joel W. Reid, Michael Sayer, "Electron spin resonance in silicon substituted apatite and tricalcium phosphate", Biomaterials, June 2005, p3-14; Joel W. Reid, Loughlin Tuck, Michael Sayer, Karen Fargo and Jason A. Hendry, "Synthesis and characterization of single-phase silicon-substituted α-tricalcium phosphate," Biomaterials, Volume 27, Issue 15, May 2006, Pages 2916-2925]. The need for high-temperature processing of the biomaterials is a drawback of this approach as well, similar to the bioglass described above.
The bioglass, calcium phosphates, and all cements in the CPC family of cement, are unstable in biological environments, and eventually dissolve, frequently providing room and a chemical environment encouraging growth of new tissue, such as bone tissue. However, in many applications, such as endodontics or orthopedic applications where the cement must have sufficient strength at all times, resorption is not desirable. The present invention is directed to non-resorbable biological cements that are based on calcium silicates.
Accordingly, there exists a need for a hydraulic cement for use in medical and dental applications that is free from aluminum and other elements/compounds which present potential toxicity problems in a biological system. Still further, there exists a need for such a hydraulic cement that is biocompatible with the surrounding tissue and system in additional respects, and that exhibits a high degree of bioactivity. Furthermore, there exists a need for such a hydraulic cement which can set and gain sufficient strength at room or near-room temperatures (such as body temperature). Still further, there exists a need for such a hydraulic cement which, when set, will exhibit substantially no resorption during lifetime of the implant Still further, there exists a need for such a hydraulic cement that develops sufficiently high strength, stability and resistance to fracture/brakage to be suitable for use as a bone substitute, in dental work, in orthopedic surgery, and in other medical and dental applications. Still further, there exists a need for such a hydraulic cement that can be placed and set under temperatures, pH levels and other conditions that are compatible with the human biological system.
The present invention provides a new composition of hydraulic cement, and methods for making and using the composition for biomedical and dental applications. The new hydraulic cement has high mechanical strength, high bioactivity, and high biocompatibility. The cement is resistant to corrosion and is stable and durable in variety of environments, including biological environments. The cement sets at room or near-room temperatures and does not resorb (dissolve) in a biological environment.
The cement of the present invention is an aluminum-free and magnesium-free phospho-silicate hydraulic cement. The cement comprises oxides of calcium, phosphorous and silicon, and excludes magnesium and aluminum in any form. Although free of magnesium and aluminum compounds, the new cement rapidly gains strength through hydration-assisted setting at room temperature and pressure. As a result, it has high early strengths, high overall compressive strength, adjustable setting times, low hydration heat, and resistance to chemical degradation.
The cement compositions comprise at least one phosphate compound and at least one calcium silicate compound. The cement of present invention preferably uses synthetic (high purity) di- and tri-calcium silicates ([2CaO.SiO2], [3CaO.SiO2]), with no aluminum. The additive powders are preferably calcium phosphates, including dicalcium phosphate or monocalcium phosphate.
In a preferred embodiment, the first of the principal components of the biocement is calcium oxide (CaO), in the range of about 45%-80% by weight of cement in the composition, preferably in the range of about 50 wt %-70 wt %. The second of the main components is silica (SiO2), in the range of about 10%-35% by weight of cement in the composition, preferably in the range of about 15 wt %-30 wt %. The calcium oxide and silica are preferably provided in combined form, as di-calcium and/or tri-calcium silicates. The third of the main components is the phosphate (preferably in the form of P2O5 or as alternative ionic form), in range of about 1%-30% by weight of cement in the composition, preferably in the range of about 3 wt %-15 wt %.
Complex chemical and physical reactions and processes take place after the hydraulic cement powder components are mixed with water, which is preferably substantially pure water. These reactions involve hydration of calcium silicate compounds and dissolution of phosphate compounds, and the precipitation of calcium phosphates, including hydroxyapatite. These reactions proceed in an alkaline environment of pH>10. The dissolution of the phosphate compounds and precipitation of calcium phosphates take place during the hydration of the calcium silicate compounds, so that the by-products of the hydration of the calcium silicate compounds, particularly calcium hydroxide, are taken up and utilized to precipitate calcium phosphate compounds. More specifically the calcium silicate compounds (mainly di-calcium silicate (C2S) and tri-calcium silicate (C3S) react with water to produce calcium silicate hydro-gel and calcium hydroxide (CH). The inorganic chemical phosphate compound reacts in-situ with the calcium hydroxide to form a high strength hydroxyapatite precipitate, which is dispersed throughout the Calcium-Silicate-Hydrate (C—S—H) matrix, therefore simultaneously removing the CH (which as noted above, is ordinarily a structurally weak component in the body of set cement).
As a result, the biocement of the present invention has enhanced functionality, in particular enhanced strength and corrosion and dissolution resistance due to the absence of CH, combined with enhanced biocompatibility and bioactivity due to the presence of HAP and/or other phosphate inclusions. The HAP inclusions produced reactively in-situ also contribute substantially to the overall compressive strength of the set cement, both directly (through bonding to the C—S—H structure) and indirectly (through removal of the structurally weak CH inclusions). Additionally, HAP is much more resistant to environmental effects than CH, rendering the CPSC of the present invention more resistant to corrosion.
Silicate nanoparticles may optionally be introduced into the cement composition of the present invention to improve mechanical, setting, and biological properties. The silicate nanoparticles may suitably be in a colloidal silica solution that is mixed with the biocement powder. Silicate nanoparticles can be mixed with the biocement powder by ball milling. The colloidal nanoparticle will speed up the hydration of calcium silicate compounds and increase mechanical strength. Also, the silicate can enhance biocompatibility and bioactivity of biocement.
Furthermore, for dental applications, radio-opaque materials may be added to the composition to enhance absorption of X-rays, for improved visibility of the cement under X-ray examination. Examples of radio-opaque materials suitable for dental applications include, but are not limited to, barium sulfate, zirconium oxide, bismuth oxide, tantalum oxide, and mixtures thereof. Radio-opacity is very desirable in the cases of dental fillings and sealings; for some applications, however, it is not necessary to have high radio-opacity, for instance, pulp capping or in many orthopedic applications.
The novel biocement of the present invention may also be used as a bioactive coating for medical devices and drug delivery vehicles. The cement coating can be deposited on the surface of a medical device at room temperature, which is advantageous by comparison with coating techniques that require elevated temperatures for deposition. Single or multiple drugs can be encapsulated into the biocement matrix using an in-situ process. A variety of coating deposition technologies, well known in the art, may be used for deposition of films of the biocement on substrates such as implants; the techniques may include, without limitation, dip-coating, spray-coating, electro-assisted coating, aerosol-coating, and combinations thereof.
a. Overview
The present invention provides novel cement compositions and methods of making them and using them in a variety of medical and dental applications. The hydraulic cement (called later BA) of the present invention has high mechanical strength, adjustable setting time, low hydration heat, resistance to degradation, high bioactivity and biocompatibility, and stability in corrosive environments.
The hydraulic cement of the present invention is obtained through a novel chemical process of in-situ formation of hydroxyapatite/calcium silicate hydrate gel composite, at room- or near-room-temperature and pressure, accompanied by the removal of CH during cement hydration, resulting in aluminum-free and magnesium-free hydraulic phosphor-silicate cement. This is accomplished by reacting the CH in-situ with phosphate ions to precipitate much stronger and chemically resistant calcium phosphate, in particular hydroxyapatite (HAP), intimately mixed with the C—S—H gel. The composite cement has high mechanical strength, as well as biocompatibility, bioactivity, and adjustable setting times. These properties do not require application of hydrothermal treatment, pressure-assisted forming, or high temperature sintering of the components. The setting time is adjusted through provision of micron-size particles of the hydrating powders, thus removing the need for early-hydration chemicals containing aluminum.
The major components of the biocement compositions, which make up approximately 60% by weight of cement in the cement composition, comprise at least one calcium silicate compound and at least one phosphate compound. Suitable calcium silicate compounds include, but are not limited to, dicalcium silicate C2S (2CaO.SiO2),tetracalcium silicate C4S (4CaO.SiO2, tricalcium silicate C3S (3CaO.SiO2) and mixtures thereof. Suitable phosphate compounds include, but are not limited to, calcium phosphates, with calcium phosphate monobasic generally being preferred. The phosphates may contain hydration water. More complex (pre-reacted) phosphates may also be used, such as many variants of the calcium phosphates. The at least one phosphate compound is preferably included in an amount sufficient to react a major portion of the calcium hydroxide that is produced by hydration of the calcium silicate compound or compounds. Other calcium compounds may be included in the cement composition, including but not limited to, calcium oxide, calcium carbonates, calcium hydroxides, and mixtures thereof. The at least one calcium silicate compound is suitably included in an amount in the range from about 30% to about 99% by weight of the cement composition, preferably in the range from about 40% to about 80%. The at least one phosphate compound is suitably included in an amount in the range from about 1% to about 70% by weight of the cement composition, preferably in the range from about 5% to about 30%. Where present, ancillary compounds are preferably included in a total amount less than about 30% by weight of the cement composition.
A significant difference from prior art cements is that the hydraulic cement of the present invention is in its preferred embodiment both magnesium-free and aluminum free, or at least substantially free of such materials, and still maintains desirable setting and set cement characteristics. By contrast, as discussed above, all Portland cement derived hydraulic cements require fast hydrating aluminum compounds such as calcium aluminates, to achieve a sufficiently high rate for the initial hydration reaction and strength buildup of the setting cement, but with negative consequence for biocompatibility.
Minor compounds that may be included in the cement compositions in present invention include, but are not limited to, calcium oxide, silicon dioxide, iron oxide, other metal oxide compound, calcium sulfate, calcium sulfate dihydrate (CaSO4.2H2O), and mixtures thereof. The minor compounds will generally make up less than 10% by weight of cement in the composition and preferably no more than 30% by weight.
For some dental applications, radio-opacity materials may be added to the biocement composition for improving absorption of X-rays. Suitable radio opacity materials may be selected from heavy metals, oxides of heavy metals and salts of heavy metals, and may include, but are not limited to, gold, silver, barium bismuth, tantalum, barium sulfate, zirconium oxide, bismuth oxide, tantalum oxide, and mixtures thereof. The radio-opaque materials will generally constitute less than 70% by weight of cement in the composition; suitably, the radiopaque substance or substances may be included in an amount in the range from about 3% to about 50% by weight of the cement composition, preferably in the range from about 10% to about 40%.
When water is mixed with the novel cement, a complicated set of reactions is initiated. The phosphate and calcium compounds quickly dissolve in water and precipitate to produce new calcium phosphate compounds, especially hydroxyapatite, when pH is above 7.0. The reaction speed is adjustable in range from 20 min to 2 days to meet to the requirements of applications, through minor change in the system chemistry and precursor morphology.
Initially, the calcium silicates react with the water to produce a calcium silicate hydrate gel (CaO—SiO2—H2O gel); however, the rate of hydration reaction of calcium silicates is slower than that of the formation of hydroxyapatite and calcium phosphates. Consequently, in the process of co-precipitating nano-size particles of calcium silicate hydrate gel fill the voids among the precipitating hydroxyapatite particles.
A key aspect of the present invention is the in-situ formation of a hydroxyapatite/calcium silicate hydrate gel composite at room temperaturse, in ordinary prepared cement paste, without a need for elevate pressures or temperatures, and in particular without a need for thermal treatment of the setting cement paste, and without a need for Al or Mg ions participating in the reaction. The formation of the C—S—H/HAP composite is accompanied by a decrease of CH content in the set cement. The resulting composite biocement material, due to its decreased CH content, provides significantly increased mechanical strength, with the calcium phosphate and hydroxyapatite acting as a reinforcement phase and calcium silicate hydrate gel forming the matrix of the composite structure.
An important aspect of the current invention is its aluminum-free composition, which provides significantly improved biocompatibility, bioactivity and safety with as compound prior cements. As noted above, soluble aluminum is highly toxic to the osteoblast and inhibits mineralization of bone, may cause dialysis dementia, renal osteodystrophy and Alzheimer's disease.
By comparison with the cement disclosed by Wagh (as discussed above), the main components of the cement of the present invention are di-calcium and tri-calcium silicates and phosphate; the cement does not include magnesium oxide. Also, mono-calcium silicate (e.g. CaSiO3) powders are not necessary in the present invention, and it is not necessary to have any "sparsely soluble oxide" powder for the setting and hardening reactions. The liquid used to hydrate (set) the cement of the present invention is substantially neutral (pure) water, without any acidic pH modifying agents being needed for the cement setting and hardening reactions; to the contrary, the pH conditions during setting in present invention are alkaline, typically above pH=10. Moreover, the hydroxyapatite in present invention is produced through in-situ chemical reaction of the phosphate powder and the calcium hydroxide that is produced by the hydration of the calcium silicates, thus introducing nano-size HAP into the composition and thereby enhancing the mechanical properties and biocompatibility and bioactivity of the set cement; these reactions do not take place in Wagh's composition.
b. Reactions and Materials
The precipitation reaction (A) of calcium phosphate apatite is as follows:
10Ca2++6PO4 3−+2OH−→Ca10(PO4)6(OH)2 (A)
where the Ca/P ratio is between 1.2 and 2.0.
The hydration reactions (B, C) of calcium silicates can be approximated as follows:
2[3CaO.SiO2]+6H2O→3CaO.2SiO23H2O+3Ca(OH)2 (B)
2[2CaO.SiO2]+4H2O.3CaO.2SiO2.3H2O+Ca(OH)2 (C)
where the calcium hydroxide CH is the hydration product which contributes to the high alkalinity of the cement. The calcium silicate hydrate is not a well-defined compound and the formula of (3CaO.2SiO2.3H2O) is only an approximate description. The ratio of CaO/Si2O is in between 1.2 and 2.3, which depends on water contain, aging time and temperature, and other factors. The high pH (pH=10-13) during hydration, in the presence of phosphate ions (PO4 3−) increases the precipitation rate of the calcium phosphate, particularly hydroxyapatite, according to the reaction (A), which in turn decreases the overall alkalinity of hydration. Consequently, a process is created which both (i) decreases the alkalinity and CH content in the setting cement; and (ii) provides a strong and bio-active HAP phase which reinforces the composite.
In order to further remove the calcium hydroxide CH during setting of the cement, and thus further enhance its mechanical strength, additional phosphate may be introduced into the cement composition, which will continue to react with calcium hydroxide to form hydroxyapatite. If the calcium phosphate compound is calcium phosphate monobasic, the following dynamic chemical reaction takes place:
3Ca(H2PO4)2+7Ca(OH)2.Ca10(PO4)6(OH)2+12H2O (D)
The calcium hydroxide, produced during the hydration reaction of calcium silicates, reacts relatively rapidly with the phosphate compounds to produce the new compound, hydroxyapatite (HAP). Importantly, the same reaction (D) also provides water, which continues to react with the calcium silicates. The water supplied through reaction (D) is an important factor in controlling the hydration reaction speed, and thus setting time, hardening time, and the final mechanical strength of the composite biocement.
To further improve mechanical strength, silica nanoparticles may be introduced into the cement composition to react with remnant calcium hydroxide and thereby further decrease CH content and alkalinity of the cement.
The hydration rate of the calcium silicates (reactions B, C) increases as setting progresses, since the phosphate compounds in biocement react with calcium hydroxide to produce hydroxyapatite and water (reaction D), thus shifting the equilibrium. Therefore, the setting and hardening time of the biocement is shortened.
In the case of ordinary Portland cement (OPC) compositions, the hydration reactions of calcium silicates results in an increase of pH to over 12. In the cement composition of the present invention by contrast, the phosphate compounds react with the calcium hydroxide and thus neutralize the pH of the cement. The calcium hydroxide is therefore only the intermediate product of the hydration of calcium silicates in biocement of the present invention.
In ordinary Portland cement (OPC), the main strength providing compound is calcium silicate hydrate (C—S—H). C—S—H is an amorphous or poorly crystalline material which forms very small particles of submicron (less than 1 um) size. The calcium hydroxide CH, on the other hand, is a well-crystallized material with a definite stoichiometry, which occupies about 20-25% of the volume of OPC cement paste. The calcium hydroxide precipitates wherever free space is available and may completely engulf the cement grains. However, as noted above, calcium hydroxide is mechanically weak and it therefore greatly reduces the mechanical strength of the cement. In present invention, the calcium hydroxide is only an intermediate product, as it reacts with the phosphate compounds to produce the hydroxyapatite and water, according to reactions A and D.
In the set biocement of the present invention, the calcium silicate hydrate (C—S—H) interlocks with the hydroxyapatite, leading to in situ formation of a composite-like structure interspersed at a nanoscale level. The hydroxyapatite thus provides a reinforcement phase while the C—S—H forms the matrix of the composite structure. As a result, both phases contribute mechanical strength to the composite. By comparison with mineral trioxide aggregate (MTA) which, as noted above, is derived from ordinary Portland Cement, the mechanical strength and corrosion resistance of the material are significantly improved, because the weak phase calcium hydroxide of the former is replaced with high strength, chemically stable hydroxyapatite (HAP). The HAP has a compressive strength (>60 MPa) which is much higher than that of calcium hydroxide (<1 MPa). Moreover, hydroxyapatite (Ca10(PO4)6(OH)2) is one of the most biocompatible and bioactive ceramics because it is similar to the mineral constituents of natural human bone and teeth. Consequently, due to the relatively large content of HAP, the presently disclosed biocement of the present invention is not only bioactive and biocompatible, but also is osteoinductive and osteogenic (i.e., it encourages bone in-growth).
As a result, the cement of the present invention is especially suited for use in medical materials and devices, such as prostheses, implants, coatings, and other surgical procedures. The biocement is self-setting, injectable, and develops high strength cement, allowing it to be used for both weight and non-weight bearing applications. The cement can be deposited in a selected location in a patient's body and then allowed to cure to a solid therein. The cement resists disintegrative washout upon contact with blood, and injection into the wound is less stressful to the surrounding tissue because of being completely biocompatible with the physiological environment. Therefore examples of bio-medical applications for biocement of the present invention include, but not are limited to, orthopedic surgery, bone repair, bone reconstruction bone filling, bone fixation and combinations thereof, such as. for example, human and veterinary percutaneous vertebroplasty, craniomaxillofacial surgery, ridge augmentation, spinal fusion cage/implant, treatment of radial fractures, treatment of temporal mandibular, joint disorders, plastic surgery and cosmetic augmentation, bone graft substitution, scaffolding, drug delivery, and variations thereof. The biocement can also be used for dental applications, such as, for example, root canal filling, root canal sealing, root perforation repair, root resorption repair, root-end filling, retrofilling materials, pulp capping, apexification, and combinations thereof. The cement may also be used as a coating on devices, in particular medical implants. Another example includes use of the cement with drugs or proteins to address the specific medical problems, e.g.,. microspheres of biocement may be designed for targeted delivery of drugs, proteins, DNA, or other medically active species to areas of interest in the body.
The cement of the present invention can also be used make composite materials including specific secondary reinforcement phases, such as fibers, aggregates, bioglasses, bioceramics, polymers, and metals, in variety of morphological forms such as particles, fibers and loops for example.
c. Testing
FTIR spectra provide essential features of the cements. There are three main regions related to the vibration frequencies of SO4, SiO4, and CO3 groups in wave number ranges 500-1300 cm−1. For the MTA samples, the sulfate absorption bands (i.e. the S—O stretching bands) at 1150-1100 cm in hydrated Portland cement are shown as a shoulder band. The bands at 960 cm−1 and 520 cm−1 are contributed by the Si—O asymmetric stretching and the Si—O out-of-plane bending vibration of SiO4 group of calcium silicate hydrate gel. Another band at 870 cm−1 is contributed by the vibration of CO3 group [refer also to the Mollah et al, "A Fourier transform infrared spectroscopic investigation of the earlyhydration of Portland cement and the influence of sodium lignosulfonate" Cement and Concrete Research 30 (2000) 267-273].
For the hydroxyapatite (HAP) (see
By comparison with MTA, the frequencies of bands of vibration and liberation modes of various functional groups representative of hydroxyapatite appear on FTIR spectra of the cement of the present invention when including 10 wt % calcium phosphate compounds. As can be seen in
In this example the phosphate silicate cement was prepared synthetically using well defined, substantially pure chemicals (as opposed to the poorly defined minerals utilized for preparation of the typical commercial Portland cements). The raw materials used were colloidal silica (50 wt % Ludox, from 3M company) for the SiO2 component, calcium hydroxide (99.9%, Sigma-Aldrich) for the CaO component, tetracalcium phosphate (Ca4(PO4)2O), and dicalcium phosphate anhydrate (CaHPO4.H2O) (Fisher). The designed composition was 65 wt % tricalcium silicate, 20 wt % dicalcium silicate, 10 wt % tetracalcium phosphate, and 5 wt % dicalcium phosphate.
A 200 g cement batch was prepared by mixing 96.32 g of colloidal silica, 160.98 g calcium hydroxide, and 300 g distilled water in a ceramic jar, followed by ball milling for 24 hours. The slurry of this mixture was dried by using a spray dryer, and then fired in high temperature furnace at 1550� C. for 1 hour to form tricalcium silicate and dicalcium silicate, after which it was naturally cooled to room temperature. The resulting cement clinker was ground to −325 sieve particle size (<45 um particle size), with an average particle size of about 10 um. 11.25 g of dicalcium phosphate anhydrate was dried in the furnace at 140� C. for 24 hours and then mixed with 20 g of the tetracalcium phosphate and with the fired cement powder (168 grams) in alcohol solution, allowed by ball milling for 24 hours. The resulting slurry was spray dried. The average particle size of the cement powder was about 10 um.
The setting time of the cement was about 4 hours. The average compressive strength after 7-day incubation at 37� C. and 100% humidity was 104 MPa, with a standard deviation of 7 MPa. The control samples of the cement without the addition of phosphates, and set under identical conditions, had an average compressive strength of 45. MPa, with a standard deviation of 5 MPa.
This example utilized a sol-gel process to prepare high-purity, aluminum-free biocement. Tetraethylorthosilicate (TEOS), Ca(NO3)2 4H2O, triethyl phosphate (TEP) were used in the sol-gel method. Ca(NO3)2 4H2O was dissolved in 1M HNO3 solution and TEOS was added to the solution with vigorous stirring to obtain a nominal composition of 70 mol % CaO-30% SiO2. After 10-15 min of hydrolysis under stirring, a homogenous sol was obtained. The sol precursor was sealed in a container, where the precursor was allowed to gel for 1 day at room temperature and aged for another day at 70� C. The dry gel powder was obtained by heating the templated gel at 600� C. in air for 1 hour (heating rate: 2� C./min). The dry powder was fired at 1400� C. for 2 hrs. The crystalline product was analyzed by X-ray diffraction (XRD). The results of XRD indicated that the product contained only the phases of tricalcium silicate and dicalcium silicate.
The biocement was obtained by mixing 75 wt % of the sintered powder with 15 wt % calcium phosphate mono-basic and 10 wt % dicalcium phosphate in planetary ball mill for 10 min. The average particle size of the cement powder was about 2 um. The properties of the resulting set biocement were evaluated as follows: compressive strength of 72 MPa and setting time of 1 hour.
The set samples of the biocement were submerged into Simulated Body Fluid (SBF) solution at 37� C. for 7 days for testing bioactivity of the biocement. The surface morphology of the cement particles was examined by SEM, and EDX analysis was performed for elemental composition. The results show that a typical (for a highly bioactive material) hydroxyapatite structure film was deposited on the surface of biocement, as shown in
In this example, biocement was prepared in the same manner as described in Example 1. The setting time of was about 1 hour to 4 hours, for a water/cement ratio of 0.25. The average compressive strength after 7-days incubation at 37� C. and 100% humidity was 104 MPa, with the standard deviation of 7 MPa, as shown in
The X-ray diffraction pattern provided in
The following procedure was used to prepare high-strength bioactive and biocompatible biocement for dental applications.
The raw materials used were colloidal silica (50 wt % Ludox, 3M) for the SiO2, calcium hydroxide (99.9%, Sigma-Aldrich) for the CaO, iron oxide (Fe2O3, 99% Fisher), calcium sulfate dehydrate (CaSO4.H2O, 99%, Fisher), Ca(OH)2, and monocalcium phosphate (Ca(H2PO4)2, 99%, sigma). The designed composition was 62 wt % tricalcium silicate (3CaO.SiO2), 18 wt % dicalcium silicate (2CaO.SiO2), 4 wt % calcium sulfate dehydrate (CaSO4.2H2O), 4 wt % calcium oxide, and 12 wt % monocalcium phosphate (Ca(H2PO4)2). A 200 g batch was prepared by mixing in 300 g distilled water in a plastic jar, followed by zriconia ball milling for 24 hours. The slurry mixture was dried using a spray dryer, and then fired in a high a temperature furnace at 1550� C. for 1 hour. It was then naturally cooled to room temperature, followed by grinding to about 10 um average particle size. 20 g of monocalcium phosphate, 8 g of calcium hydroxide, and 8 g of calcium sulfate dehydrate were mixed with the fired cement powder in alcohol solution by ball milling for 4 hours. The slurry was dried by using spray a dryer.
The setting time of the cement prepared as described was around 2 hours, for a water/cement ratio of 0.21. The compressive strength following a 7-day incubation at 37� C. and 100% humidity was 110 MPa, with a standard deviation of 7 MPa. Control samples of the cement, without the addition of phosphates and set under identical conditions, had an average compressive strength of 48 MPa, with a standard deviation of 4 MPa. The X-ray diffraction pattern provided in
This biocement paste was injectable, gray in color, and suitable for dental applications, such as a root-end filling material, retrofilling material, pulp capping, apexification, and the sealing of perforations. To make a white color biocement for dental applications requiring color control (e.g. for cosmetic reasons), all of the preparation steps described above were repeated exactly, except that the iron oxide was excluded from the composition. The properties of the white variant of the biocement were essentially the same as the properties of the gray variant.
This example compared the bioactivity of prior mineral trioxide aggregates (MTA) to a cement in accordance with the present invention having 10% calcium phosphate.
The paste samples were prepared by mixing the cement powder with distilled water at the water/cement ratio of w/c=0.25. The cement paste was filled into a cylinder mold having a 1-inch diameter and 2-inch height. The samples were incubated at 100% humidity and the procedure described by Li, et at, [Apatite formation induced by silica gel in a simulated body fluid. J Am Ceram Soc 75 (1992), pp. 2094-2097] was followed without use of any organic species, and with pH adjusted to 7.4 with 7.5% NaHCO3 solution.
All samples were immersed in SBF solution at 37C for 7 days. The samples were then washed with distilled water and dried for SEM observations, which are illustrated in
This example illustrates procedure for making a dental cement that incorporates a radio-opaque material.
The fired cement powders were prepared as described in Example 3. Zirconia (ZrO2, Zircoa, USA) was chosen as the radio-opaque material for dental application, because zirconia is biocompatible and is used for orthopedic implant devices. 80 g of the biocement powder and 20 g of zirconia powder were mixed in a powder mixer for 20 min.
X-ray tests showed clear visibility of the modified biocement, demonstrating that the dental cement with zirconia radio-opaque is suitable for dental applications.
This example showed that nanoparticle silicates can be used as beneficial additives in the biocement of the present invention. Suitable silicate nanoparticle material can be purchased from commercial suppliers, such Lodux colloidal silica. Also, silica nanoparticles can easily be synthesized through a sol-gel process, e.g. decomposition of TEOS.
The biocement powder was prepared as described in Example 2 above. 20 wt % colloidal silicate (Ludox) was mixed with biocement powders to form the cement paste. The results were a compressive strength of 110 MPa, and a setting time of 40 min.
The set samples were immersed in SBF solution at 37� C. for 3 days to test bioactivity. The surface morphologies were examined by SEM and EDX analysis of elements. The SEM results showed that a characteristic hydroxyapatite structure film was deposited on the surface of biocement. The film was confirmed to be hydroxyapatite by EDX and XRD analysis.
It is to be recognized that various alterations, modifications, and/or additions may be introduced into the constructions and arrangements of parts described above without departing from the spirit or ambit of the present invention as defined by the appended claims.
|Cited Patent
|Filing date
|Publication date
|Dec 14, 1967
|May 5, 1970
|Kuneo Taguchi
|Water settable quick setting cement composition and a method of making same
|Jan 16, 1979
|Nov 25, 1980
|G-C Dental Industrial Corporation
|Dental compositions
|Apr 23, 1993
|May 16, 1995
|Loma Linda University
|Tooth filling material and method of use
|May 16, 1995
|Jun 23, 1998
|Loma Linda University
|Tooth filling material and method of use
|Jun 2, 1995
|Sep 22, 1998
|The Trustees Of The University Of Pennsylvania
|Bioactive material template for in vitro synthesis of bone tissue
|Sep 18, 2000
|Feb 11, 2003
|The University Of Chicago
|Chemically bonded phospho-silicate ceramics
|Aug 6, 2004
|Aug 1, 2006
|Dentsply International, Inc.
|Method and product for phosphosilicate slurry for use in dentistry and related bone cements
|May 10, 2002
|Jan 2, 2003
|Pugh Sydney M.
|Synthetic biomaterial compound of calcium phosphate phases particularly adapted for supporting bone cell activity
|Jan 3, 2002
|Aug 28, 2003
|Primus Carolyn M.
|Dental material
|Sep 12, 2005
|Apr 13, 2006
|Leif Hermansson
|Resorbable ceramic compositions
|Title not available
|Diarra, M. et al., Elaboration and evaluation of an intraoral controlled release dilvering system, Biomaterials, 19, pp. 1523-1527 (1998).
|Driessens, F. et al., Formulation and setting times of some calcium orthophosphate cements: A pilot study, J. of Materials Science: Material in Medicine, 4, pp. 503-508 (1993).
|Fridland, M. et al., MTA solubility: A long term study, JOE 31:5, pp. 376-379 (May 2005).
|Hamanishi, C., et al., Self-setting, bioactive, and biodegradable TTCP-DCPD apatite cement, J. of Biomedical Materials Research, 32, pp. 383-389 (1996).
|Mindess, S. et al., Concrete, Civil engineering and engineering mechanics series, pp. 76-111 (1981).
|Mitchell, P. et al., Osteoblast biocompatibility of mineral trioxide aggreagate, Biomaterials 20, pp. 167-173 (1999).
|Oonishi, H. et al., Particulate bioglass compared with hydroxyapatite as a bone graft substitute, Clinical Orthopaedics and Related Research, 334, pp. 316-325 (1997).
|Persson, B., Seven-year study on the effect of silica fume in concrete, Elsevier, pp. 139-155 (1998).
|Torabinejad, M. et al., Physical and chemical properties of new root-end filling material, J. of Endodontics, 21:7, pp. 349-353 (1995).
|Citing Patent
|Filing date
|Publication date
|Aug 18, 2009
|Jan 1, 2013
|Innovative Bioceramix, Inc.
|Hydraulic cement compositions and methods of making and using the same
|Jun 16, 2010
|Nov 10, 2015
|Department Of Biotechnology
|Sealbio: a novel non-obturation regenerative technique of endodontic treatment
|Jun 16, 2010
|Sep 13, 2012
|All Indian Institute of Medical Sciences
|Sealbio: a novel non-obturation regenerative technique of endodontic treatment
|U.S. Classification
|106/35, 106/691, 433/224, 424/682, 106/781, 106/806, 106/717, 424/603, 106/690, 424/602, 623/23.62
|International Classification
|Cooperative Classification
|European Classification
|Mar 4, 2009
Owner name: INNOVATIVE BIOCERAMIX INC., CANADA
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Free format text: CHANGE OF ADDRESS;ASSIGNOR:INNOVATIVE BIOCERAMIX, INC.;REEL/FRAME:022796/0095
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Sexually transmitted infections and associated socio-demographic and behavioural factors in women seeking primary care suggest Madagascar's vulnerability to rapid HIV spread
Version of Record online: 7 JUL 2008
DOI: 10.1046/j.1365-3156.2001.00690.x
Tropical Medicine & International Health
Volume 6, Issue 3, pages 202–211, March 2001
Additional Information
How to Cite
Behets, F. , Andriamiadana, J. , Rasamilalao, D. , Ratsimbazafy, N. , Randrianasolo, D. , Dallabetta, G. and Cohen, M. (2001), Sexually transmitted infections and associated socio-demographic and behavioural factors in women seeking primary care suggest Madagascar's vulnerability to rapid HIV spread. Tropical Medicine & International Health, 6: 202–211. doi: 10.1046/j.1365-3156.2001.00690.x
Publication History
- Issue online: 7 JUL 2008
- Version of Record online: 7 JUL 2008
- Abstract
- Article
- References
- Cited By
- STIs;
- sex workers;
- behavioural risk factors;
- socio-demographic factors;
- Symptomatic women;
- Madagascar
OBJECTIVES To examine sexually transmitted infections (STIs) and associated socio-demographic and behavioural factors in women seeking care for genital discharge syndrome in Antananarivo, Madagascar.
METHODS One thousand and sixty-six consecutive symptomatic women were interviewed and examined; bacterial vaginosis (BV), vulvovaginal candidiasis, trichomoniasis (TV), cervical infection (CI) due to chlamydial or gonococcal infections, and syphilis seroreactivity were determined by laboratory diagnosis. Associations between STIs and individual characteristics were evaluated using bivariate and logistic regression analyses.
RESULTS The prevalence of BV, TV, CI, and syphilis seroreactivity was, respectively, 85%, 16%, 49%, 16% in 94 prostitutes; 70%, 18%, 30%, 13% in 96 occasional sex traders; and 53%, 24%, 17%, and 4% in 876 general women. CI was independently and positively associated with a symptomatic partner, new sex partner in last 3 months, unfaithful partner, prostitution, joblessness and being < 25 years old. Syphilis was associated with low schooling, young age at coital debut, sex trading, and > 1 sex partner in the previous 3 months.
CONCLUSIONS These high STI rates and associated characteristics suggest the local vulnerability to rapid HIV spread and show the need for prevention efforts that involve youth, prostitutes, occasional sex traders, sex clients, and men who have concurrent sexual partnerships.


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Marc Jacobs supports maternal health via limited-edition teeApril 28, 2016
U.S. fashion label Marc Jacobs is using its brand visibility to show that every mother counts.
U.S. fashion label Marc Jacobs is using its brand visibility to show that every mother counts.
Together with Global Citizen, Italian fashion label Gucci's Chime for Change charity is calling on Beyoncé Knowles-Carter fans to stand in formation against poverty, injustice and gender inequality.
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Immunization & Health Forms
You are hereHome/ Students/ Counseling and Wellness/ Health & Wellness/ Immunization & Health Forms
Immunization Requirements & Optional Health Form
In accordance with Massachusetts state law, The Boston Conservatory requires that undergraduate, graduate, and other visiting students (such as MEIP) demonstrate immunity to specific communicable diseases.
Prior to arriving on campus, students must submit an Immunization History Form, signed/stamped by a licensed medical provider.
- Only the official Boston Conservatory form will be accepted, and all required immunizations must be complete. If complete immunization information is not submitted, the student will not be allowed to attend classes.
- Students may be allowed to complete the second and/or third shot of certain immunizations upon arrival, if necessary.
- For a medical exemption, please attach a letter from a licensed medical provider, stating that there is a medical reason why the student cannot receive each of any missing vaccinations.
- For a religious exemption, please attach the Religious Exemption Form.
- In order to decline the Meningococcal vaccine, please review the information provided and attach the Meningococcal Waiver Form.
- Please note that Massachusetts law does not allow for philosophical exemptions, even if signed by a medical provider.
If the Optional Health Form is submitted, Counseling & Wellness Services will contact the student in order to provide resources and support.
Please download the Immunization History and Optional Health Forms in the language you prefer:
Immunization Record Request Form
All requests to receive a copy of a current or former student's immunization record must be submitted through the form below. By law, immunization and other health records are kept on file for seven years. At that time they are destroyed.
- Please allow 1–2 weeks from the date this request is received for records to be sent.
- If your immunization records are not available, it is recommended that you contact the medical facility where you received your immunizations. You may also have immune titers performed to document immunity.
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text:
Marblehead, Massachusetts
Commute to Downtown Salem
Daily errands do not require a car.
About your score
This location has a Walk Score of 91 out of 100. This location is a Walker's Paradise so daily errands do not require a car.
This location is in Marblehead. Nearby parks include Seaside Park, Seaside Park and William I Hammond Park.
Explore how far you can travel by car, bus, bike and foot from this location.
Bus lines:
0.0 mi
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This location is in the city of Marblehead, MA. Marblehead has an average Walk Score of 49 and has 19,808 residents.Learn More About Marblehead


text:
Applications are invited for the following posts in the ICMR funded project:Title:Hospital Based Cancer Registry: PI:Prof. Dr. Punita Lal
Applications are invited for the following posts in the CST funded project: PI:Prof. U.K. Misra
Applications are invited for the following posts in the DST funded project: PI: Dr. Amita Aggarwal
Requirement of PhD Scholar: Dept: PathologyFaculty: Dr Niraj Kumar, Addl. Prof
Walk-In-Interview:Empanelment of Guest Faculty for College of Nursing(Advt No: I/64/Acad/2015-16)
Faculty Recruitment 2016 (I-61/ER/ACAD/2015-16)Advertisement ||
Instructions & Application form
Announcement for taking PhD students:Dr. Rakesh & Dr.Amita Aggarwal, Dept. of Gastroenterology & Immunology
Advertisement for adhoc Senior Residents (HS), Med Phys Residents & Demonstrators for the year 2016
Applications are invited for the post of Secretarial Assistant:PI: Dr. Rakesh Aggarwal, Dept. of Gastroenterology
Advertisement for part time / external teachers for the College of Nursing, SGPGI, Lucknow


text:
Why It's (Finally) Time for Restaurant Workers to Celebrate the Holidays
The holidays are a distant, hazy memory for most, which is why this is the time people in the hospitality industry actually get to enjoy themselves.
The holidays are a distant, hazy memory for most, which is why this is the time people in the hospitality industry actually get to enjoy themselves.
The guys have some feelings about happiness and success.
He says it's all about nostalgia.
A look at the most disruptive restaurant trend over the past decade.
These are a few of Eric Ripert's favorite things.
"Mid-recipe, we also snacked on toasted bread that had been used to soak up some of the fat from the sliced marrow medallions roasting in the oven."
Marietta, Colonie, and ABC Cocina are all serving the wild, seasonal 'shroom.
Silk suits, Air Jordans, strapless dresses, and more sartorial choices from last night's big event.
New York had an exceptionally strong showing, with Le Bernardin, wd~50, Blue Hill, Mission Chinese, Del Posto, and Momofuku among the winners.
Here's what moved (what shaked, too) on the 2013 list.
Get ready for 11,500 more square feet of French-ness.
Plus: Hugh Jackman at Kittichai, and more, in this week's roundup.
Maison Kayser will be on baguette duty from here on out.
Fancy ice-cream sandwiches, deconstructed s'mores, and tequila-spiked snow cones.
An important list of important restaurants.
Kogi BBQ founder Roy Choi remembers his first time.
Four hours of oppression at Blanca.
Also, she fights her way through a nasty cold with anchovies on toast and a lot of gelato.
"I have this kind of devilish — you say devilish? — look."
Like his recent announcement in D.C., he wants to focus more on Le Bernardin.


text:
The Great Perhaps
The Great Perhaps
W. W. Norton & Company, Paperback, 9780393304565, 414pp.
Publication Date: April 12, 2010
List Price: $14.95*
* Individual store prices may vary.
Buy at Local Store
Enter your zip code below to purchase from an indie close to you.
Buy Here
The sky is falling for the Caspers, a family of cowards. When the parents decide to separate, this family is forced to appreciate the cloudiness of this modern age.
About the Author
Joe Meno is the founder of BrickJournal, a print and online LEGO(r) fan magazine. He has organized and run LEGO fan events, acted as an advisor on LEGO projects, and helped design LEGO sets.


text:
Articles tagged aqualung
19 Oct 2010 // 6:30 AM
An unfairly named, unfairly shunned, and completely unhip genre, adult alternative, in my opinion, is producing some of the best new music these days, and you don't have to be a project manager with two kids and a suburban home to enjoy it. Here I examine three examples of the best records in said genre from this year.READ more
20 Apr 2010 // 10:00 PM
There's a refreshing aspect to the personal sound of Magnetic North that many artists, when being so introspective, completely neglect: the soul need not be permanently tortured.READ more
22 Oct 2008 // 11:00 PM
Caution must be taken to avoid listening too hard lest you risk inescapable boredom.READ more
6 Apr 2005 // 11:00 PM
Aqualung is (unfortunately?) not a Jethro Tull cover band. It's more like what might happen if Coldplay had a brain.READ more
Blesst Chest "Blesst Chest Theme Song" (audio) (premiere) // Music
The Chairman Dances "Dorothy Day and Peter Maurin" (audio) (premiere) // Music
National Park Radio 'The Great Divide' (album stream) (premiere) // Music
Kendra Erika "The Truth Never Lies" (video) (premiere) // Music
Culture Belongs to the Alien in 'Spirits of Xanadu'
// Moving Pixels
"The symbols that the artifact in Spirits of Xanadu uses are esoteric -- at least for the average Western gamer. It is Chinese culture reflected back at us through the lens of alien understanding.READ the article


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Do you have to be stick thin to wear these jeans? Student creates eco-denim collection using bits of WOOD
It sounds like a job for Twiggy - modelling a pair of jeans made from wood.
Fashion student Dawn Ellams branched out from traditional design to create the super soft trousers as part of a PhD project.
Dawn, 29, uses pulp from eucalyptus trees to create a material which is then spun into yarn to make the crazy clothes.
Amber Lorimer models Dawn Ellams' sustainable fashion jeans made from wood fibre
She said: 'They don't give you splinters and they're just as soft as any other pair of trousers.'
Dawn, a PhD student at Heriot-Watt's School of Textiles in Galashiels, Scottish Borders, came up with the idea during her research into sustainable fashion.
Her 'eco-jeans' only use one fifth of the water, energy and chemicals needed to make a conventional pair of jeans.
She said: 'The wood gets mushed up into a coffee-like mixture and that is turned into white stringy stuff which we then chop up and spin it into a yarn.
Dawn, a student at Heriot-Watts School of Textiles in Galashiels, Scottish Borders created the eco-friendly jeans with pulp from eucalyptus trees
'I'm looking into sustainable fashion for my PhD - and I've been working with Tencel, the company who make the fibre. So I thought I would make some cottonless jeans.
'Before they're turned into jeans they just look like any normal woven or knitted fabric, and the cloth is softer than cotton - so they are a very comfortable fabric.
'I think it is quite wacky that the jeans are made from wood. I really think of them as a good niche product that should definitely have a place in the market.
'They've passed health and safety - there's no way you'll be getting any splinters from them. The wood is completely melted down and dissolved, so they are not scratchy.
'The jeans are absolutely fine to be washed as well, they're made for the high street, so they're not going to shrink or turn back into a tree.
The denim effect is created using screen printing rather than the intense washing and dying process that goes in to making regular jeans
The trousers get the denim look by digital printing rather than the usual intensive washing and dyeing methods associated with jean manufacturing.
Making one pair of regular denim jeans uses an average of 42 litres of water and can also require up to 15 dyeing vats and an array of harmful chemicals.
But Dawn's green jeans, which cost around £27 to produce, could revolutionize the process by saving water and drastically reducing carbon emissions.
She added: 'My aim is to make a whole collection - I've also been working on another item I've called the 'Eucalyptus dress'.'
The aim now is to eventually sign up suppliers with a view to bringing the product to the High Street - touch wood.
Dawn says: 'They don't give you splinters and they're just as soft as any other pair of trousers,'
As well as eucalyptus pulp fashion brands are using hemp, organic and recycled cotton and even bamboo to create our favourite skinnies.
Monkee Genes organic cotton £30 asos.com
Levi's WATERLESS Skinny jeans £95
Recojeans.com Low-Rise Skinny
Kuyichi.com recycled cotton Nova Skinny
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The fabric of America is held together by our small towns. Some towns have violet festivals and some celebrate strawberries and some jump frogs. Lyons, NY, once upon a time, was the peppermint capitol of America and to celebrate their heritage and affinity with peppermint Lyons holds Peppermint Days including a tractor show. The 13th annual tractor show is also home to what is believed to be the only tractor square dance in New York State. [Read more…]
Grasstravaganza 2014 promotes love of the land through understanding
MORRISVILLE, NY — Aldo Leopold once said, "When we see land as a community to which we belong, we may begin to use it with love and respect." This sentiment was an overarching theme at the three-day Grasstravaganza 2014 event that brought 150 farmers, ag educators and conservation professionals together to peer deeply into soil health, pasture productivity and creating wealth by nurturing the land. [Read more…]
Raising cattle for the future, today
Rich Brown says five generations on all sides of his family tree have been in some kind of livestock business, so it's natural that he'd continue the tradition.
Brown's involvement with beef cattle began at his parents' farm in Antwerp, NY. "I was working off the farm," he said. "My parents were no longer milking, and the pastures were growing up in brush. I decided it made sense to put beef cattle there." Brown put five registered Angus heifers on the farm in 1995, and in 2000, moved to Port Byron, NY, to grow the herd. [Read more…]
Cover crops prove to be a good management tool for vegetable growers
Cover crops should be a part of every vegetable farmer's toolbox. That's the message that Thomas Björkman, Associate Professor of Vegetable Crop Physiology with Cornell University explained to attendees of a vegetable grower's meeting and workshop that took place near Fort Plain, NY.
Since vegetable production compromises soil health, which directly affects productivity, building and maintaining soil is a priority for vegetable producers.
"One management goal that is central for many vegetable farmers is maintaining good tilth, which is accomplished in part by always feeding soil microorganism with fresh organic matter," Björkman explained. "Cover crops can provide that organic matter between vegetables." [Read more…]
Sparrow Soap and how it grew
Billy goats are the butt of many farm-related jokes, but without their services, many enterprises using goats and their by-products would quietly disappear from the scene. Bucks are usually relegated to the farthest corner of the farm, but here at Kingdom Kids Family Farm, they are housed in a barn (aptly named Man Cave), located directly behind the main barn. For those unfamiliar with goats, bucks emit a unique odor during the breeding season which most people rank somewhere between unacceptable to intolerable. This characteristic stands in stark contrast to the product produced by farm owner Michelle Lyon and her partner Sue Barry. Since 2011, they have been manufacturing cosmetic soap using goat milk as a critical ingredient. [Read more…]
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I've posted this problem on the Aquoid support forum four days ago and not rec'd any response. Problem started after updating to Suffusion 4.4.6!
The Specifics are the following:
How can we adjust the post "Title" container?
The tiles on the magazine view have changed sizes and are no longer equal.
Navigation bar below header has lost all it's drop-downs.
The tiles in the page of posts have reverted to white-they have lost chosen color.
The Social Sharing buttons at the bottom of each post will not load.
Please, please somebody...anybody, help.
(link to the site is http://copymoz.com/)


text:
Wikipedia:WikiProject Outlines/Drafts/Outline of common law
From Wikipedia, the free encyclopedia
The following outline is provided as an overview of and topical guide to common law:
What type of thing is common law?[edit]
Common law can be described as all of the following:
Branches of common law[edit]
History of common law[edit]
- Main article: History of common law
General common law concepts[edit]
i dnt know why you can edit it because peo-ple can right really stupid things. GO AVALANCHE!
Persons influential in common law[edit]
I'm Latvian , I like beer and dances and also Janu siers.
See also[edit]
External links[edit]
Find more about
Common law
at Wikipedia's sister projects
|Definitions from Wiktionary
|Media from Commons
|News from Wikinews
|Quotations from Wikiquote
|Texts from Wikisource
|Textbooks from Wikibooks
|Learning resources from Wikiversity


text:
San Antonio Vfw Post 4815
1. Post Vfw 8541
I just called this VFW and they were not able to help with a different location of a VFW, nor a street name...really that is absurd, I mean I would …
2. VFW Post 9174
not much of a canteen dirty glasses and sinks not friendly at all would not recommend this place to anyone
3. VFW Post 76
10 10th StSan Antonio, TX 78215
4. VFW Post #8936
3001 Guadalupe StSan Antonio, TX 78207
5. V F W Westside Post
3001 Guadalupe StSan Antonio, TX 78207
6. Motor Trnspt Post 1533 V F W
107 Elmhurst AveSan Antonio, TX 78209
7. V F W Post 837
4436 Valleyfield StSan Antonio, TX 78222
8. VFW Post 7108 Helotes, TX
8795 Fm 1560 NSan Antonio, TX 78254
9. VFW Post 6970
9655 N State Highway 16Poteet, TX 78065
10. Vfw Post 7110
600 Peace AveNew Braunfels, TX 78130
11. McQueeney VFW Post 9213
275 Gallagher RdMc Queeney, TX 78123
12. VFW Post 8111
Serving the San Antonio Area.
13. US Post Office-Brooke Army Med Ctr Cs
Thsi is the best state of the art hospital. I was never just a number. The people/staff there is gerat, understanding.\r If u have to be at a hospi…
14. US Post Office
An absolutely wonderful post office. The employees are super helpful and courteous. Yes, there is sometimes a line, but they seem to do everything t…
15. US Post Office
Very Good Customer service!! I go there all the time to ship my package. I like the service. The great thing about them is they open late and i can …
16. US Post Office
I've been to every post office on this side of town. Hands down these folks are the friendliest and most efficient. If they were all like this the…
17. US Post Office
Well, after seeing all these bad reviews here on yelp for this Encino post office, they have redeemed themselves as far as I am concerned! Sylvester…
18. US Post Office
The worst customer service around. The mailman never comes to the door to deliver certified mail so getting the mail is nearly impossible. Had to …
19. US Post Office
Once again, not enough workers to go around.
20. US Post Office
The United States Post Office has a well-deserved reputation for terrible customer service. They continue to fail at delivering mail in a timely man…
21. US Post Office
I am highly upset...with the post office on Broadway in s.a,tx I went in to order the key for my mailbox on the 3rd of August today on the 12th they…
22. US Post Office
I have been in business for quite a while now, shipped out hundreds of packages. shipped out of many USPS facilities. I have never experienced such …
23. US Post Office
a poor station. clerks are rude, drivers misdelivered mail, long lines only one station open, also supervisor blows off the customer whenever compla…
24. US Post Office-Countryside Plaza
USPS says that this 13428 San Pedro location is not run by USPS although everything you see would indicate that it is. I delivered a package to this…
25. US Post Office
i am beyond angry and frustrated with this office. The incompetence is beyond real. I submitted a change of address in early December, effective J…
26. US Post Office-Carry On
I can' believe how rude the men there were. I had a 10:30 passport appointment so I was able to observe the mood and workers while waiting. There we…
27. US Post Office-Frost Bank Tower
100 W Houston St Ste 100San Antonio, TX 78205
28. US Post Office
615 E Houston StSan Antonio, TX 78205
29. US Post Office
1140 S Laredo StSan Antonio, TX 78204
30. US Post Office
2400 McCullough AveSan Antonio, TX 78212


text:
The process of buying a new Toyota car or truck can seem overwhelming if you don't know where to begin. Edmunds.com can get you started on the right track with a convenient directory of Toyota car dealerships in and around Norwood, New Jersey. Compare online price quotes on the new or used car, truck, SUV, minivan, or wagon of your choice to locate the best deals. Edmunds.com makes it easy to find trusted Toyota car dealers in Norwood, saving car buyers time and money on what will be an important purchase.
Non Display Review Name "Contacted Rockland Toyota via internet and received price quote. Robert H (sales agent) greeted me at the dealership and printed a copy of the price q"... Read more Review by: STVB49
Non Display Review Name "It was an awesome and overwhelming experience closing a deal with Pedro S at Westchester Toyota. As a first time buyer, I did not have any hard time u"... Read more Review by: carlo12
Non Display Review Name "Picked up my new 2015 Tundra on Friday and I absolutely love it. My sales rep and sales manager went above and beyond to get me my truck. The delivery"... Read more Review by: Joko91
Non Display Review Name "From start to finish i had an excellent car buying experience! Robert, Victor S & Dayden are awesome! I love my brand new Toyota Venza XLE! " Read more Review by: arabella1
Non Display Review Name "I had a great experience with Neil at Glen Toyota. I went to the dealership to "see what my options are" and left less than 2 hrs later with a brand n"... Read more Review by: Aleksandra_S
Non Display Review Name "Great experience. Sales rep Jean was very knowledgeable. He was very receptive of my needs (didn't try to sell me cars out of my price range) and nego"... Read more Review by: hobopetey


text:
by Lionel Goldstein
May 14, 19, 21, at 7:30 P.M
May 15 and 22 at 3:00 P.M.
at the Rose Firebay
Starring Ken Farrell & Gerard Pauwels
Directed by Katie Horwitz
Tickets at BCT box office , $20.....on sale NOW!
Purchase tickets at box office, by phone , or online.
114 E. Kirkwood, 812-323-3020, www.bctboxoffice.com
Two men,strangers to each other , both in love with the same woman for 50 years, meet for the first time at her grave site, and sparks fly! Halpern is the Jewish man she married and Johnson; who is not Jewish, was her first love. With warmth and candor, this bittersweet drama explores the complex nuances of marriage and friendships, secrets and lies.
Talkbacks after May 14 and May 19 performances
Facilitated by Darrell Stone.
Full house on opening night! Some seats remain at the BCT box office for the rest of the run.


text:
Flow: The Psychology of Optimal Experience
Harper Collins, Oct 13, 2009 - Psychology - 336 pages
Psychologist Mihaly Csikszentmihalyi's famous investigations of "optimal experience" have revealed that what makes an experience genuinely satisfying is a state of consciousness called flow. During flow, people typically experience deep enjoyment, creativity, and a total involvement with life. In this new edition of his groundbreaking classic work, Csikszentmihalyi demonstrates the ways this positive state can be controlled, not just left to chance. Flow: The Psychology of Optimal Experience teaches how, by ordering the information that enters our consciousness, we can discover true happiness and greatly improve the quality of our lives.
What people are saying - Write a review
User ratings
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Flow: A Path to HappinessUser Review - Beth. - Borders
Besides having more vowels in his name than any other researcher in the field of positive psychology, Mih�ly Cs�kszentmih�lyi is probably best known for his book "Flow". So what exactlty is flow and ... Read full review
Flow explains the conclusions from the many years of thorough research on what makes us feel happy and totally engaged with life. It starts with the assumption that the universe was not designed with the comfort of human beings in mind, actually it is empty, called and chaotic. In order to be happy humans create meaning, set goals and order their consciousness. That way we are in control of our lives, regardless of the material conditions, regardless of the caprices of the universe.
The function of consciousness is to represent information about what is happening outside and inside the organism in such a way that can be evaluated and acted upon by the body.
The more one can influence what goes in and out of his consciousness, more he is in flow, feeling happy, fulfilling great and important goals. The author, Mr. Csikszentmihalyi, argues that the product of consciousness, which is the subjective experience, is not just one of the dimensions of life, it is life itself.
Some chapters are a bit dry and overloaded with statistical information, nevertheless the book is valuable source of inspiration and knowledge about how we can achieve harmony and higher, more complex and more satisfying level of existence.
Other editions - View all
Flow: The Classic Work on how to Achieve Happiness
Mihaly Csikszentmihalyi
No preview available - 2002


text:
BBC Twitter account delete Mourinho quote: "I don't see a problem selling Mata to Man United, they are no threat"
- January 22, 2014
- Comments0
The BBC's 606 Twitter account has attracted attention for posting and deleting a tasty quote attributed the Jose Mourinho on the Juan Mata deal with Manchester United.
The BBC 606 tweet read:
Mourinho: "I don't see a problem selling Mata to Man United, they are no threat to us. What are your thoughts on this #CFC & #MUFC fans?
No sooner had the tweet gone out, but it was instantly retracted by the flagship British broadcasters. It all begged the question had someone jumped the jump? Or alternatively, was the quote false?
A copy of the BBC's juicy deleted tweet suggesting Juan Mata is leaving Chelsea for Man United imminently is below.
Grab more information on: ChelseaJose MourinhoJuan MataManchester United
Odds on next game: Bournemouth: 7/2, Draw: 11/4 & Manchester United: 8/11


text:
Student Jane Diange shares what makes Charleston Law a unique place to attend law school
The Princeton Review ranks Charleston School of Law professors in Top 10 for student satisfaction
Schedule a visit and discover what makes the Charleston School of Law unique
Charleston School of Law
81 Mary Street
Charleston, SC 29403
Mailing Address:
P.O. Box 535
Charleston, SC 29402
Tuesday, Aug. 9 - Orientation Day 1
Wednesday, Aug. 10 - Orientation Day 2
Thursday, Aug. 11 - Orientation Day 3
Monday, Aug. 15 - Classes begin for the fall semester
Monday, Sept. 5 - Labor Day
Charleston School of Law students volunteer with VITA to provide free tax preparation for people with low-to-moderate incomes.
© 2016 Charleston School of Law. All Rights Reserved. | Site Map | ABA Required Disclosures | Gainful Employment Disclosures | Academic Catalog | Student Handbook


text:
One True ThingHD Closed Captioning
Carl Franklin
Open iTunes to preview, buy and download this film.
About the Film
Join Academy Award®-winners Meryl Streep and William Hurt, along with Renee Zellweger, for an unforgettable look at the pleasure, pain and ultimate joy of being a family. When crisis confronts Katherine and George Gulden, they turn to their grown daughter, Ellen, for support. An ambitious New York journalist, Ellen at first rejects the idea of returning home. But once there, Ellen embarks on a journey of self-discovery that will change her forever. Uplifting and humorous, One True Thing is filled with the power of genuine passion.
Customer Reviews
Misleading Plot summary and trailer
My wife and I were looking for an uplifting and humorous film, and the plot summary describes this film in those exact words. Almost all the humour is in the trailer. The film explores the angst and moral dilemmas surrounding people terminally ill with Cancer. There is a tiny hint of an uplift in the final scene, but after watching it, we felt dark & sad. Very well put together, and poigniant, but not to be watched if you don't want to explore the morality of end of life issues. This is a serious warning for anyone suffering with cancer, or caring for someone with it, that the case for ending someone's life is powerfully advocated in this film.
One True Thing
This is an AMAZING film, a heartfelt look at the human condition! Maryl streep is, as always, outstanding & this is my favourite of her films. Renne is surprisingly good & her charactors journey is very relatable. One true thing is a good old weepie to watch with the girls, that leaves you with something a bit bit more profound to ponder upon!
Good movie
I enjoyed this film a lot. Meryl Streep is excellent as a busy housewife and mother who is diagnosed with cancer. Her husband is a professor and writer played by William Hurt who is in total denial about his wife's illness. Renee Zellweger plays the daughter who goes back home to look after her mother, who she didn't really relate to. Of course, as time passes she starts to bond with her and realise that things aren't always what they seem. It's a lovely film and has you dabbing at your eyes from time to time. It poses the question 'would you?'. Watch it and see.
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- £7.99
- Genre: Drama
- Released: 1998
- © 1998 Universal City Studios Productions, Inc. All Rights Reserved.